ClinVar Miner

Submissions for variant NM_000100.3(CSTB):c.29A>C (p.Gln10Pro) (rs569851503)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724370 SCV000224147 uncertain significance not provided 2014-12-02 criteria provided, single submitter clinical testing
GeneDx RCV000724370 SCV000240866 uncertain significance not provided 2017-02-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CSTB gene. The Q10P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q10P variant is not observed at a significant frequency in large population cohorts; however, limited data are available (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Q10P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000638323 SCV000759817 uncertain significance Progressive myoclonic epilepsy 2018-08-21 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 10 of the CSTB protein (p.Gln10Pro). The glutamine residue is weakly conserved and there is a moderate physicochemical difference between glutamine and proline. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with CSTB-related disease. ClinVar contains an entry for this variant (Variation ID: 193045). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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